Immunosuppressive agents are widely used in the treatment of autoimmune disease and in treating or preventing transplantation rejection, including the treatment of graft-versus-host disease (GVHD). Common immunosuppressive agents include azathioprine, corticosteroids, cyclophosphamide, methotrexate, 6-mercaptopurine, vineristine, and cyclosporin A.
In general, none of these drugs are completely effective, and most are limited by toxicity. For example, cyclosporin A, a widely used agent, is significantly toxic to the kidney, in addition, doses needed for effective treatment may increase the patient's susceptibility to infection by a variety of opportunistic invaders.
The compound triptolide, obtained from the Chinese medicinal plant Tripterygium wibrdii (TW), and certain derivatives and prodrugs thereof, have been identified as having immunosuppressive activity, e.g. in the treatment of autoimmune disease, and in treating or preventing transplantation rejection, including the treatment of graft-versus-host disease (GVHD). Triptolide and certain derivatives and prodrugs thereof have also been reported to show anticancer activity. Such derivatives and prodrugs of triptolide have provided benefits relative to native triptolide in areas such as pharmacokinetics or biodistribution, e.g. by virtue of differences in lipid or aqueous solubility, or via their activity as prodrugs; however, their biological activity is often significantly less than that of native triptolide.